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Poster Discussion - Non-metastatic NSCLC and other thoracic malignancies

1522 - A Comprehensive Model of Genetic-Features Predicts Outcome of Personalized Adjuvant Treatment in Resected EGFR-mutant Stage II-IIIA NSCLC: Results from a Phase 3 Trial (CTONG 1104-ADJUVANT)

Date

29 Sep 2019

Session

Poster Discussion - Non-metastatic NSCLC and other thoracic malignancies

Presenters

Yi-Long Wu

Citation

Annals of Oncology (2019) 30 (suppl_5): v585-v590. 10.1093/annonc/mdz258

Authors

Y. Wu1, S. Liu1, Q. Wang2, W. Mao3, L. Wu4, Y. Shen5, Y. Cheng6, C. Chen7, L. Xu8, J. Wang9, H. Liu10, H. Bao11, Y. Chen12, X. Zhang13, Z. Chen1, H. Yan1, J. Yang13, Y.W. Shao11, Q. Zhou13, W. Zhong14

Author affiliations

  • 1 Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN
  • 2 Thoracic Surgery, Fudan University Affiliated Zhongshan Hospital, Shanghai/CN
  • 3 Thoracic Surgery, Cancer Hospital of University of Chinese Academy of Sciences, , 310022 - Hangzhou/CN
  • 4 Medical Oncology, Hunan Cancer Hospital, 410006 - Changsha/CN
  • 5 Thoracic Surgery, The Affiliated Hospital of Medical College Qingdao University, Qingdao/CN
  • 6 Department Of Thoracic Oncology, Jilin Cancer Hospital, Changchun/CN
  • 7 Thoracic Surgery, Fujian Medical University Union Hospital, 350001 - Fuzhou/CN
  • 8 Thoracic Surgery, Jiangsu Cancer Hospita, Nanjing/CN
  • 9 Thoracic Surgery, Peking University People’s Hospital, 100044 - Beijing/CN
  • 10 Thoracic Surgery, Liaoning Cancer Hospital & Institute, Shenyang/CN
  • 11 Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto/CA
  • 12 Medical Department, Geneseeq Technology Inc., Nanjing/CN
  • 13 Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou/CN
  • 14 Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, 0086 - Guangzhou/CN
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Resources

Abstract 1522

Background

Results of the ADJUVANT trial established adjuvant gefitinib as an optimal choice for EGFR-mutated stage II-IIIA NSCLC patients. However, clinical benefit varied among patients. To investigate this heterogeneity, we performed comprehensive tumor genomic analyses on these patients. Here, we report the predictive MEDUSA model (Multiple-biomarker Evaluation to Determine the Utilization of Specific Adjuvant therapy) that can guide clinical decision of adjuvant therapy.

Methods

171 baseline specimens from ADJUVANT (n = 95, gefitinib arm; n = 76, vinorelbine plus cisplatin [VP] arm) underwent targeted sequencing (Geneseeq 422-gene panel). Predictive biomarkers were identified by Cox regression with gene-by-treatment interactions, and a multi-gene composite score was developed to compare the benefits of these treatments.

Results

EGFR mutations were confirmed in all cases. TP53, NKX2-1, CDK4, MYC and RB1 were identified as predictive biomarkers. Specifically, gefitinib-favoring biomarkers include TP53 exon4/5 mutations (interaction HR [iHR] 0.33, 95% CI 0.12-0.93, p = 0.035), and copy number gain of NKX2-1 (iHR 0.26, 95% CI 0.098-0.68, p = 0.006), CDK4 (iHR 0.14, 95% CI 0.025-0.77, p = 0.024) and MYC (iHR 0.10, 95% CI 0.011-0.98, p = 0.048). RB1 alterations strongly favored VP (iHR 4.07, 95% CI 1.56-10.53, p = 0.004). The MEDUSA model was developed based on the above, and stratified patients into 3 groups: Strong Gefitinib-favoring (SG, n = 60), Moderate Gefitinib-favoring (MG, n = 87), and VP-favoring (VP, n = 24). Notably, the SG group demonstrated significant OS benefit with adjuvant gefitinib as well: HR of OS was 0.44 (95% CI 0.2-0.98, p = 0.04).Table: 1441PD

MEDUSA ScoremDFS (m)2y DFS(%)HR(95% CI)P
SG≤-0.534.5 vs 9.170.3 vs 11.00.21 (0.1-0.43)<0.0001
MG-0.5 to 0.532.8 vs 20.767.5 vs 41.00.61 (0.35-1.07)0.08
VP≥0.519.3 vs 34.241.6 vs 69.23.07 (0.98-9.52)0.04

Conclusions

Incorporating alterations in TP53, NKX2-1, CDK4, MYC and RB1, MEDUSA score could guide personalized adjuvant therapy for resected stage II-IIIA EGFR-mutant NSCLC patients.

Clinical trial identification

NCT01405079; Release at July 29. 2011.

Editorial acknowledgement

Legal entity responsible for the study

Chinese Thoracic Oncology Group (CTONG).

Funding

AstraZeneca Roche.

Disclosure

Y. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. H. Bao: Full / Part-time employment: Geneseeq Technology Inc. Toronto. Y. Chen: Full / Part-time employment: Geneseeq Technology Inc. Nanjing. Y.W. Shao: Full / Part-time employment: Geneseeq Technology Inc. Nanjing. All other authors have declared no conflicts of interest.

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